Diabetic Neuropathy – Causes, Types, Signs and symptoms

Diabetic Neuropathy

Also called: Diabetic Nerve Disease, Diabetic Nerve Damage

Summary

Diabetic neuropathy is nerve damage that is caused by diabetes. It is not completely known why this common diabetic complication develops. Contributing factors include uncontrolled glucose (blood sugar) and damage to blood vessels, which supply nutrients and oxygen to the nerves.

Types of diabetic neuropathy include:

  • Peripheral neuropathy. Mainly affects the limbs.

  • Autonomic neuropathy. Affects heart rate, breathing, digestion, perspiration, blood pressure, sexual function, and bladder and bowel functions.

  • Focal neuropathy. Affects a single nerve, usually in face, eyes or feet.

  • Proximal neuropathy. Mainly affects the hips, thighs and buttocks.

About 60 to 70 percent of diabetic individuals have neuropathy, the U.S. National Institutes of Health estimates. It is most likely to occur in people who have a long history of diabetes and uncontrolled glucose. However, diabetic neuropathy has also been found in people with prediabetes.

Nerves carry messages between the brain and spinal cord and the other parts of the body. The most common symptoms of neuropathy include pain, tingling and numbness in an affected limb. Other indicators may include blurred vision, impaired hearing or sexual dysfunction, but sometimes there are no symptoms.

A key to treatment is glycemic control. Keeping glucose at normal or near-normal levels will help lessen or even eliminate the symptoms of neuropathy. For the pain of neuropathy, a physician may recommend prescription or over-the-counter medications or topical creams.

Treatment can reduce the symptoms, but there is no known cure for neuropathy. Ways to prevent or slow the progression of the condition include control of glucose, blood pressure and cholesterol. Scientists are continuing to research the causes of neuropathy and testing potential treatments.

About diabetic neuropathy

Diabetic neuropathy is a group of nerve disorders related to diabetes. Nerves run throughout the body connecting the spinal cord to muscles, skin, blood vessels and organs. Some nerves provide information to the brain from these body areas; others carry signals to the body areas from the brain.

Damaged nerves are unable to transmit correct signals. The result is impaired sensation, motor function or autonomic (regulatory) functions, causing symptoms such as pain, numbness, weakness or sexual dysfunction. Nerve injuries may be temporary or permanent, and the symptoms may change over time.

Diabetic neuropathy, a common complication in patients with diabetes, is generally caused by high levels of glucose (blood sugar) and poor blood flow. Other causes of neuropathy may include autoimmune disorders, immune system disorders such as AIDS, injury, alcohol abuse, poor diet, genetic factors, thyroid disorders, kidney diseases, nerve diseases such as Guillain-Barre syndrome, infections and chemotherapy drugs. Nondiabetics can develop neuropathies, as well, such as carpal tunnel syndrome or cranial neuralgias.

Not all diabetes patients will experience nerve damage. Neuropathy is most likely to occur in people who have:

  • A long history of diabetes
  • Difficulty controlling glucose (unstable diabetes)
  • High levels of blood fats)
  • High blood pressure (hypertension)

Diabetic neuropathy can affect people with type 1 diabetes, type 2 diabetes and lesser-known forms of the disease, such as maturity-onset diabetes of the young (MODY) and latent autoimmune diabetes of adulthood (LADA). In addition, diabetic neuropathy can already be present in people with prediabetes. In fact, symptoms of neuropathy (such as tingling, pain or numbness in the hands, feet or legs) can be the first indication that a person has prediabetes or diabetes.

About 60 to 70 percent of diabetic patients have some form of neuropathy, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) estimates. Chances of developing nerve damage increase the longer a person has diabetes. There is no apparent difference among racial groups for developing neuropathy. This condition is more common in:

  • People over 40
  • Males
  • Overweight individuals
  • Smokers

Neuropathy can occur anywhere in the body, including:

  • Limbs (legs, feet, arms, hands)
  • Senses (touch, sight and hearing)
  • Systems (cardiovascular, neurologic, respiratory and digestive)
  • Functions (bladder, bowel and sexual)

Research continues into the causes of diabetic neuropathy, ways to prevent it and how to cure it. Experimental treatments using nerve growth factors and gene therapy may offer a promising future for recovery from diabetic neuropathy.

Types and differences

Diabetic neuropathy is classified by physicians in different ways. The type of neuropathy is determined by the:

  • Location of the damaged nerves
  • Which body part or system is affected
  • Type of nerves involved
  • Symptoms

The symptoms vary depending on the nerves damaged. The condition may be asymmetric (one side of the body) or symmetric (both sides). In addition, the damage may affect one nerve (mononeuropathy) or multiple nerves (polyneuropathy). The most common type of neuropathy is a symmetric polyneuropathy. A physician will determine the type of neuropathy based on medical history, physical examination and test results.

In type 1 diabetes, neuropathy may occur after many years of poorly controlled glucose (blood sugar). Symptoms may go unnoticed at first, but over time they become more severe. In type 2 diabetes, symptoms of neuropathy usually appear more quickly and may be present at the time of diagnosis.

There are several forms of diabetic neuropathy that affect the body in different ways. Certain neuropathies damage the motor nerves, resulting in muscle weakness or poor coordination. Other neuropathies affect the sensory nerves, causing pain or numbness. Neuropathy can also affect the nerves that control regulatory functions such as sweating and digestion. The symptoms that occur reflect the type of neuropathy and the severity of the damage. The most common forms of neuropathy include:

  • Peripheral neuropathy. The most common form of diabetic neuropathy, peripheral neuropathy affects the peripheral nerves connecting the central nervous system to the limbs. Damage may occur in sensory or motor nerves or both, causing problems with movement and sensation. It usually develops in stages with a gradual progression of symptoms.

    In the beginning, the patient with peripheral neuropathy may experience tingling and pain that comes and goes. As the neuropathy progresses, the pain becomes stronger and more constant. In the final stages, the pain is replaced with loss of feeling. This stage is the most dangerous as the patient may not be able to feel an injury, which can lead to more serious complications, such as infections and foot ulcers.
  • Autonomic neuropathy. This disease involves damage to the nerves that help control the regulatory or involuntary systems of the body. The nerve damage can cause difficulties with heart rate, blood pressure, breathing and sweating. It may affect digestion, and is known as gastroparesis when it affects the vagus nerve serving the stomach). Problems also may occur with bladder, bowel and sexual functions. Autonomic neuropathy sometimes causes hypoglycemia unawareness, a condition in which a person has trouble sensing low blood sugar. Unlike peripheral neuropathy, autonomic neuropathy does not usually cause outward pain, making it more difficult to diagnose. The symptoms may be overlooked or thought to be related to a different condition.

  • Focal neuropathy. A less common form of nerve damage in people with diabetes, focal neuropathy affects a single nerve or group of nerves. The most common problems occur with vision, facial weakness and pain in the torso, leg or head. Although the symptoms may be more painful, they usually do not last longer than a period of several weeks or months. Focal neuropathy usually appears in older diabetic individuals with mild diabetes.
PeripheralAutonomicFocal
Affects multiple nerves, usually connecting to limbsAffects multiple nerves connecting to organs and systemsAffects single nerves usually in torso, leg or head
Problems with motor weakness or sensation throughout the bodyProblems with regulatory or involuntary body functionsProblems isolated to body area specific to damaged nerves
Gradual progression of symptoms with possible long-standing effectsGradual progression of symptoms with possible long-standing effectsSudden onset or symptoms usually with short-term effects

There are other, less common neuropathies that differ slightly from the major forms. Generally, the nerve damage is more localized in these neuropathies, resulting in a fairly specific pattern of influence. These neuropathies include:

  • Proximal neuropathy (also known as lumbosacral plexus neuropathy)
    • Affects thighs, hips, buttocks or legs
    • Asymmetrical (occurs on one side of the body)

  • Femoral neuropathy
    • Affects front of thigh
    • Muscle weakness with pain
    • More common in type 2 diabetes
    • Symptoms disappear over time

  • Thoracic or lumbar radiculopathy
    • Similar to femoral neuropathy but affects chest or abdomen
    • More common with type 2 patients
    • Symptoms disappear over time

  • Motor neuropathy
    • Affects skeletal muscles involved in movement (e.g., walking)
    • Leads to muscle weakness
    • Rare in diabetic neuropathy

  • Neuropathic arthropathy (Charcot foot)
    • Causes difficulty positioning the foot
    • Leads to possible dislocation and fractures
    • May heal over time, but foot remains deformed

  • Compression neuropathy
    • Caused by pressure on nerves (compression)
    • Most common form is carpal tunnel syndrome
    • Causes pain, swelling, tingling, numbness or impaired movement
    • May cause foot drop when it affects the peroneal nerve of the leg

  • Cranial neuropathy
    • Affects a cranial nerve (12 pairs of peripheral nerves connected to the brain rather than the spinal cord)
    • Most commonly affects the nerves controlling eye movement
    • May also affect vision, hearing, smell, taste, facial sensation or tongue movement

Some forms of neuropathy, such as carpal tunnel syndrome, are common in people who do not have diabetes.

When neuropathy cannot be attributed to diabetes, injury, alcoholism or another cause, it may be labeled chronic idiopathic axonal polyneuropathy. Research has suggested that many of these cases may be caused by prediabetes or other impairments in glucose metabolism.

As indicated, there are many forms of diabetic neuropathy with different symptoms. Physicians review the medical history, conduct a physical examination and perform diagnostic tests to determine the type of neuropathy and plan a course of treatment.

Risk factors and potential causes of diabetic neuropathy

Physicians and scientists are not sure what causes diabetic neuropathy. It is thought that several factors contribute to the disorder. High levels of glucose (blood sugar) contribute to chronic nerve damage. The extra sugar in the body appears to react chemically with the nerves or cells around the nerves. This reaction damages the nerves, causing poor transmission of signals and pain in most cases.

Studies also have shown that poor circulation or blood flow may contribute to neuropathy. High blood glucose (hyperglycemia) damages the blood vessels that carry oxygen and nutrients to the nerves. Without healthy blood flow, these nerves become damaged and die.

Other factors that may contribute to diabetic neuropathy include:

  • Long duration of diabetes
  • High fat (lipid) levels in the blood
  • Mechanical injuries to nerves
  • Genetics or inherited traits such as body type and cholesterol
  • Smoking or use of alcohol

It is thought that there is no one cause for diabetic neuropathy. It is believed that a combination of factors present in patients with diabetes contributes to the development of the condition. Scientists are continuing to study glucose, protein and chemical reactions to more fully understand the causes of diabetic neuropathy.

Recent research into diabetic neuropathy includes these findings:

  • U.S. and Japanese scientists have linked diabetic neuropathy to malfunctioning bone marrow cells that make insulin, a glucose-controlling hormone normally produced in the pancreas. They found that only those nerve cells that merged with the abnormal marrow cells had neuropathy.
  • European researchers have found autoantibodies (self antibodies) linked to autonomic neuropathy in people with type 1 diabetes. The work suggests that neuropathy can in some cases be an autoimmune disorder, in which the body mistakenly attacks itself.

Scientists hope that such research into the origins of diabetic neuropathy could eventually lead to treatments.

Signs and symptoms

Not everyone with diabetic neuropathy experiences symptoms. Among those who do, signs and symptoms vary depending on the nerves affected and their connection in the body. Some neuropathies affect motor movements and sensation, and others cause problems with bodily functions.

TypeInitial
symptoms
Symptom
progression
Onset
Peripheral (affects  nerves in
the limbs)
Tingling Burning Numbness Loss of balance/
coordination

Impaired sleep and fatigue
Sensitive to touch Muscle weakness Serious infection Gangrene AmputationGradual Worse
at night
Autonomic
(affects organ systems)
Dizziness

Low blood pressure Excess sweating Poor bladder control
Fainting

Heart rate irregularities Bladder/bowel problems Sexual dysfunction Stomach problems (nausea, poor digestion) Hypoglycemia unawareness
Gradual
Focal
(affects one nerve or group of nerves)
Blurred vision Mild facial weakness Ankle or foot weaknessDouble vision Facial paralysisSudden, but can resolve

There are considerable differences between the types of diabetic neuropathy. The initial signs vary in the way they first appear and how they progress in severity. However, once the symptoms become evident, the patient should seek medical attention. Physicians will be able to recommend the appropriate treatment and monitor the neuropathy to avoid further complications.

Diagnosis methods

Diagnosis of neuropathy is based on medical history, symptoms and a physical examination. Additional tests may be done to determine the type or extent of damage to the nerves.

When obtaining a medical history, the physician will consider the following factors:

  • Length of time with diabetes
  • Time since initial awareness of symptoms
  • Glucose (blood sugar) levels
  • Smoking and alcohol use
  • Family history of diabetes
  • Blood pressure
  • Levels of cholesterol

In reviewing symptoms, the physician will focus on:

  • Description of the symptoms
  • Change of symptoms over time
  • Location of the problems
  • Description of the type of discomfort, such as pain, numbness or tingling sensations
  • Weakness in feet, legs, arms or hands
  • Dizziness or fainting
  • Nausea or vomiting
  • Problems with urination or bowel movements
  • Sexual response and function
  • Problems with vision or hearing
  • Speech or swallowing difficulties
  • Problems with temperature or perspiration
  • Exercise patterns
  • Any other contributing factors

After review of the medical history and symptoms, the physician will conduct a physical examination. An evaluation of the feet will be included to assess feeling and circulation. A neurological examination may be be performed to evaluate muscle control, sensation and reflexes. Muscle strength, balance and coordination can also be measured using standardized tests.

Several diagnostic tests may be administered to determine the extent of nerve or muscle damage due to the neuropathy, including:

  • Nerve conduction velocity (NCV). Small electrodes are placed on the arms and legs and a low-power electric current is sent along the nerve. These pulses create a tingling sensation and usually are not painful. The physician checks for a slow or weak transmission of the current which indicates damage to that nerve.

  • Electromyography (EMG). Small, thin needles are inserted into muscles and the responses are recorded on an EMG machine. Although there may be some pain when the needle is inserted, it usually becomes less painful as the test is conducted. No electrical shocks or injections are given through the needle. The needles measure slower or weaker responses indicating muscle damage as the result of neuropathy.

  • Quantitative sensory testing (QST). In this test, various hot, cold and vibrating stimulations are placed on the body to measure sensation. The individual indicates when any sensation is felt as a result of the stimulation. There are no electrical shocks or needles in this test. The responses are used to evaluate the function of the small and large nerve endings, which may be damaged from neuropathy.

Other tests that may be used in the diagnosis and management of diabetic neuropathy include:

  • Ultrasound. This test uses high-frequency sound waves to obtain images of the body. It allows physicians to view internal organs, such as the kidneys and bladder, and their functions. An ultrasound can be used to view the bladder and urinary tract for problems associated with autonomic neuropathy.

  • Gastric emptying study. This test uses a small amount of radioactive material (tracer) to allow physicians to track food as it progresses through the gastrointestinal tract. Several hours after the patient eats a meal containing the tracer, a scanner is placed over the stomach that measures the amount of radioactivity in the stomach. This test may help to diagnose digestive problems common with autonomic neuropathy, such as gastroparesis.

  • Nerve biopsy or skin biopsy. A minor surgical procedure is performed to obtain a sample for diagnosis of various disorders. It is used to evaluate a sample of nerve or skin tissue. A skin biopsy is common, but a nerve biopsy is more complicated and used only in certain circumstances such as research settings. A biopsy may help physicians identify nerve degeneration and confirm specific conditions found in neuropathy.

Based on the diagnostic tests, a physician may refer the patient to specialists for further tests and treatment. These specialists include:

  • Neurologist (for nervous system disorders)
  • Gastroenterologist (for digestive disorders)
  • Urologist (for genitourinary tract disorders)
  • Orthopedist (for skeletal and muscle disorders)
  • Podiatrist (for foot care)
  • Ophthalmologist(for eye care)
  • Audiologist (for hearing)

Once neuropathy has been diagnosed, it is important for the patient to receive extended care and medical treatment. With close monitoring, the patient may be able to reduce the symptoms or neuropathy and avoid further complications.

Treatment and prevention

Because there are several forms of neuropathy, the treatment will vary according to the systems affected and the symptoms. Treatment of the underlying condition is a priority. In the case of diabetes, this includes controlling glucose (blood sugar).

Keeping glucose within the physician-prescribed range may help prevent or delay the onset of neuropathy. Studies have shown that patients with type 1 diabetes who controlled their glucose (glycohemoglobin A1C below 7 percent) reduced their risk of peripheral neuropathy by 60 percent. Improving glucose control may cause increased pain at first. With time, however, a more stable glucose level will result in less pain and fewer neuropathy symptoms. Better control of glucose means better health.

Preventive treatment of diabetic neuropathy may also include:

  • Proper diet and weight control

  • Good skin care and foot care

  • An exercise program to build strength and control glucose

  • Avoidance of smoking, because the damage to circulation increases the risk of foot problems and other disorders

  • Restriction of alcohol, because alcohol is a nerve toxin and can interfere with glucose control

  • Control of high blood pressure

  • Close monitoring of diabetes by medical professionals

The second focus of treatment for diabetic neuropathy is relief of symptoms. Although symptoms vary greatly, pain is one of the most common complaints. The U.S. Food and Drug Administration (FDA) has approved two drugs for relief of diabetic nerve pain: pregabalin (Lyrica), an anticonvulsant (seizure medication) that is also used to treat fibromyalgia and post-shingles pain, and the antidepressant duloxetine (Cymbalta), a serotonin and norepinephrine reuptake inhibitor (SNRI).

The American Society of Pain Educators and Johns Hopkins University School of Medicine released in 2006 what they called the first definitive consensus guidelines for treating diabetic nerve pain. As first-line treatments, they recommended duloxetine, pregabalin, controlled-release oxycodone (an opioid) and tricyclic antidepressants.

The FDA has advised that antidepressants and anticonvulsants may increase the risk of suicidal thinking in some patients. Possible side effects of pregabalin include weight gain, blurry vision and dizziness, and the FDA advises diabetic patients to monitor their skin because pregabalin causes skin sores in animals. According to the FDA, people should not take duloxetine if they have uncontrolled narrow-angle glaucoma, have serious liver or kidney disease (e.g., diabetic nephropathy), are taking monoamine oxidase inhibitors (a class of antidepressants) or are taking triptans (migraine drugs).

Other medications sometimes recommended by physicians to ease the pain of diabetic neuropathy include other anticonvulsants, other opioids (narcotic painkillers), local anesthetics such as lidocaine and anti–inflammatories such as aspirin.

Analgesic creams, such as those containing capsaicin, may be rubbed on the skin to reduce pain in a muscle or joint. These creams contain ingredients that can produce a hot, cold or numbing sensation to calm the nerve endings and lower discomfort. Research has suggested that supplements of an antioxidant called alpha lipoic acid and an amino acid derivative called carnitine may ease diabetic nerve pain.

Researchers are conducting clinical trials of several medications that may one day be available to treat diabetic neuropathy or its complications, such as foot ulcers. Several studies have suggested that an investigational class of drugs called aldose reductase inhibitors may reduce diabetic nerve damage.

Treatment for other symptoms of neuropathy may include:

  • Medications for any infections, digestive or blood pressure problems

  • Medications or other treatments for sexual dysfunction

  • Continence training, biofeedback, medications or other treatments for bladder or bowel problems, such as overactive bladder

  • Physical therapy

  • Adaptive equipment to help with motor or sensory problems

  • Splints or braces for conditions such as carpal tunnel syndrome or Charcot foot

  • Nutritional supplements

  • Psychological counseling for emotional difficulties

If noninvasive treatments fail, surgery may be recommended in some cases, such as nerve decompression for peripheral neuropathy or foot surgery for Charcot arthropathy.

Patients may also wish to ask their physician about electronic light energy units, such as monochromatic infrared energy (MIRE), that can be used in clinics or at home. Studies into the effectiveness of such treatments for diabetic neuropathy have produced mixed results.

Neuropathy can be a serious complication in diabetes, leading to pain, weakness and failure with body systems. It is important for all patients with diabetes to prevent complications and to continue to have their neuropathy monitored by medical professionals.

Gene therapy might one day lead to prevention or a cure. Clinical trials are investigating whether manipulating genes may prevent, halt or reverse diabetic neuropathy.

Questions for your doctor

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about diabetic neuropathy:

  1. Do I have or am I at risk of developing diabetic neuropathy?
  2. What else might be causing my pain, tingling, numbness or other symptoms?
  3. What tests for neuropathy might I undergo, and what do they involve?
  4. What do my test results show? What type or types of neuropathy do I have?
  5. Is my neuropathy exacerbated by a condition other than diabetes?
  6. How can my neuropathy affect me?
  7. What are my treatment options, and which do you recommend?
  8. If lifestyle improvements, glucose control and medications don’t help, is surgery an option for me?
  9. What is the expected course of my condition?
  10. Will I need to see a neurologist or other specialists?
  11. What can I do to prevent or reduce my risk of neuropathy?
  12. Can I do anything to avoid complications of neuropathy such as sexual problems or foot conditions?
  13. Are there any recent breakthroughs in gene therapy or other research into diabetic neuropathy that could benefit me?
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